Insurer Market Structure and Variation in Commercial Health Care Spending

ObjectiveTo examine the relationship between insurance market structure and health care prices, utilization, and spending.MethodsRegression models are used to estimate the association between insurance market concentration and health care spending, utilization, and price, adjusting for differences in patient characteristics and other market-level traits.ResultsInsurance market concentration is inversely related to prices and spending, but positively related to utilization. Our results imply that, after adjusting for input price differences, a market with two equal size insurers is associated with 3.9 percent lower medical care spending per capita (p = .002) and 5.0 percent lower prices for health care services relative to one with three equal size insurers (p < .001).ConclusionGreater fragmentation in the insurance market might lead to higher prices and higher spending for care, suggesting some of the gains from insurer competition may be absorbed by higher prices for health care. Greater attention to prices and utilization in the provider market may need to accompany procompetitive insurance market strategies.     

Tricyclic alkylamides as melatonin receptor ligands with antagonist or inverse agonist activity

This work reports the design and synthesis of novel alkylamides, characterized by a dibenzo[a,d]cycloheptene nucleus, as melatonin (MLT) receptor ligands. The tricyclic scaffold was chosen on the basis of previous quantitative structure-activity studies on MT1 and MT2 antagonists, relating selective MT2 antagonism to the presence of an aromatic substituent out of the plane of the MLT indole ring. Some dibenzo seven-membered structures were thus selected because of the noncoplanar arrangement of their benzene rings, and an alkylamide chain was introduced to fit the requirements for MLT receptor binding, namely, dibenzocycloheptenes with an acylaminoalkyl side chain at position 10 and dibenzoazepines with this side chain originating from the nitrogen atom bridging the two phenyl rings. Binding affinity at human cloned MT1 and MT2 receptors was measured by 2-[125I]iodomelatonin displacement assay and intrinsic activity by the GTPgammaS test. The majority of the compounds were characterized by higher affinity at the MT2 than at the MT1 receptor and by very low intrinsic activity values, thus confirming the importance of the noncoplanar arrangement of the two aromatic rings for selective MT2 antagonism. Dibenzocycloheptenes generally displayed higher MT1 and MT 2affinity than dibenzoazepines. N-(8-Methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-ylmethyl)propionamide (4c) and -butyramide (4d) were the most selective MT2 receptor antagonists of the series, with MT2 receptor affinity comparable to that of melatonin and as such among the highest reported in the literature for MLT receptor antagonists. The acetamide derivative 4b produced a noticeable reduction of GTPgammaS binding at MT2 receptor, thus being among the few inverse agonists described.     

Characterization of WRSs2 and WRSs3, new second-generation virG(icsA)-based Shigella sonnei vaccine candidates with the potential for reduced reactogenicity

Live, attenuated Shigella vaccine candidates, such as Shigella sonnei strain WRSS1, Shigella flexneri 2a strain SC602, and Shigella dysenteriae 1 strain WRSd1, are attenuated principally by the loss of the VirG(IcsA) protein. These candidates have proven to be safe and immunogenic in volunteer trials and in one study, efficacious against shigellosis. One drawback of these candidate vaccines has been the reactogenic symptoms of fever and diarrhea experienced by the volunteers, that increased in a dose-dependent manner. New, second-generation virG(icsA)-based S. sonnei vaccine candidates, WRSs2 and WRSs3, are expected to be less reactogenic while retaining the ability to generate protective levels of immunogenicity seen with WRSS1. Besides the loss of VirG(IcsA), WRSs2 and WRSs3 also lack plasmid-encoded enterotoxin ShET2-1 and its paralog ShET2-2. WRSs3 further lacks MsbB2 that reduces the endotoxicity of the lipid A portion of the bacterial LPS. Studies in cell cultures and in gnotobiotic piglets demonstrate that WRSs2 and WRSs3 have the potential to cause less diarrhea due to loss of ShET2-1 and ShET2-2 as well as alleviate febrile symptoms by loss of MsbB2. In guinea pigs, WRSs2 and WRSs3 were as safe, immunogenic and efficacious as WRSS1.     

Can Chiari malformation negatively affect higher mental functioning in developmental age?

Numerous studies on adults have confirmed that the cerebellum has a role in processing higher brain functions, and evidence of this role has emerged more recently in developmental age as well. Various types of congenital lesion are associated with neuropsychological impairments and behavioral changes that can sometimes even give rise to a picture of autism. Acquired cerebellar lesions (especially tumors and stroke) in children of normal intelligence have enabled different neuropsychological profiles to be identified, depending on the cerebellar site involved. In Chiari malformation, the cerebellar structures are squeezed and crowded inside the posterior fossa and along the time this could generate various kinds of cognitive and behavioral disorders. Currently available data remain inconclusive, however, and prospective longitudinal studies on sizable series will be needed to ascertain whether and to what degree Chiari malformations may negatively affect mental functioning in developmental age.     

Prospective validation of the provisional criteria for the evaluation of response to therapy in childhood‐onset systemic lupus erythematosus

Objective

To prospectively validate the provisional criteria for the evaluation of response to therapy in children with systemic lupus erythematosus (SLE).

Methods

In this multicenter study, childhood‐onset SLE patients (n = 98; 81 girls, 17 boys, 50% white, 88% non‐Hispanic) were followed every 3 months for up to 7 visits (total number of visits 623). The 5 childhood‐onset SLE core response variables were obtained at the time of each visit: 1) physician assessment of overall disease activity, 2) parent assessment of patient well‐being, 3) Child Health Questionnaire, 4) proteinuria, and 5) global disease activity measure score, as measured by the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or the Systemic Lupus Activity Measure (SLAM). Physician‐rated relevant changes in the disease course (clinically relevant improvement, no change in disease, or worsening) between visits served as the criterion standard. Mixed models were used to assess the diagnostic accuracy of the 4 highest‐ranked provisional definitions of response to therapy.

Results

There were 89 episodes of clinically relevant improvement between 2 consecutive visits, and 448 episodes without improvement. Irrespective of the choice of the global disease activity measure (ECLAM, SLAM, SLEDAI), sensitivities of all 4 highest‐ranked definitions were low (all ≤31%), whereas their specificities were excellent (all >88%). Using logistic models, alternative definitions can be developed with both 80% sensitivity and specificity.

Conclusion

The provisional criteria of response to therapy in childhood‐onset SLE may have considerably lower sensitivity than previously reported. Additional validation in clinical trials is necessary to further evaluate the measurement properties of the provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology criteria for response to therapy in children with SLE.     

Toward clinically usable CAD for lung cancer screening with computed tomography

Objectives

The purpose of this study was to define clinically appropriate, computer-aided lung nodule detection (CAD) requirements and protocols based on recent screening trials. In the following paper, we describe a CAD evaluation methodology based on a publically available, annotated computed tomography (CT) image data set, and demonstrate the evaluation of a new CAD system with the functionality and performance required for adoption in clinical practice.

Methods

A new automated lung nodule detection and measurement system was developed that incorporates intensity thresholding, a Euclidean Distance Transformation, and segmentation based on watersheds. System performance was evaluated against the Lung Imaging Database Consortium (LIDC) CT reference data set.

Results

The test set comprised thin-section CT scans from 108 LIDC subjects. The median (±IQR) sensitivity per subject was 100 (±37.5) for nodules?≥?4 mm and 100 (±8.33) for nodules?≥?8 mm. The corresponding false positive rates were 0 (±2.0) and 0 (±1.0), respectively. The concordance correlation coefficient between the CAD nodule diameter and the LIDC reference was 0.91, and for volume it was 0.90.

Conclusions

The new CAD system shows high nodule sensitivity with a low false positive rate. Automated volume measurements have strong agreement with the reference standard. Thus, it provides comprehensive, clinically-usable lung nodule detection and assessment functionality.

Key Points

? CAD requirements can be based on lung cancer screening trial results. ? CAD systems can be evaluated using publically available annotated CT image databases. ? A new CAD system was developed with a low false positive rate. ? The CAD system has reliable measurement tools needed for clinical use.